Infection with influenza A virus (IAV) predisposes the host to secondary bacterial infections. Exposure of PMNs to IAV inhibits a variety of cell activation steps. In the proposed project, the effect of IAV on the activation of trimeric and monomeric G-proteins will be studied. The effect of IAV on the normal movement of these G-proteins between PMN membranes and the non-membrane compartments will be studied. The effect of IAV on activation steps other than those directly involved in G- proteins will also be examined. Other studies will examine agents that reverse IAV-induced PMN end-stage dysfunction to determine if they can correct alterations in G-proteins and other activation processes. The goal of these studies is to determine the mechanisms by which IAV causes PMN dysfunction. These studies will also provide information for developing drugs to prevent or treat superinfection due to influenza and other viruses.